Cytotoxic and cytostatic effects of digitoxigenin monodigitoxoside (DGX) in human lung cancer cells and its link to Na,K-ATPase

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Naira F Z SchneiderCláudia M O Simões

Abstract

Cardiac glycosides (CGs) are natural compounds widely used to treat several cardiac conditions and more recently have been recognized as potential antitumor agents. They are known as Na,K-ATPases ligands, which is a promising drug target in cancer. In this study, the short and long-lasting cytotoxic effects of the natural cardenolide digitoxigenin monodigitoxoside (DGX) were evaluated against two non-small cell lung cancer lines (A549 and H460 cells). It was found that DGX induced cytotoxic effects in both cells and the apoptotic effects were more pronounced on H460 cells. In long-term analysis, using the clonogenic and the cumulative population doubling (CPD) assays, DGX showed a reduction of cell survival, after 15days without re-treatment. To better understand DGX effects in A549 cells, several assays were conducted. In cell cycle analysis, DGX caused an arrest in S and G2/M phases. This compound also increased the number of cells in subG1 phase in a concentration- and time-dependent manner. The presence of β-galactosidase positive cells, large nucleus and flattened cells indicated senescence. Additionally, DGX inhibited Na,K-ATPase activity in A549 cells, as well as in purified pig kidney and in human red blood cell membran...Continue Reading

Citations

Feb 23, 2020·Anti-cancer Drugs·Laurita BoffCláudia Maria Oliveira Simões
Mar 17, 2018·Frontiers in Pharmacology·Naira F Z SchneiderMarc Diederich
Jan 19, 2021·Molecular and Cellular Biochemistry·Naira Fernanda Zanchett SchneiderCláudia Maria Oliveira Simões
Jan 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·M V M NovaisM C Oliveira
Jun 16, 2021·The Journal of Membrane Biology·Gisele Capanema de OliveiraVanessa Faria Cortes
Jan 1, 2020·ACS Omega·Jennifer MunkertAndré L B de Barros
Oct 31, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·E R GomesM C Oliveira

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